LGR4遺伝子の無意味な変異は,いくつかのヒトの病気と他の特徴と関連しています
Unnur Styrkarsdottir1, Gudmar Thorleifsson, Patrick Sulem
1deCODE Genetics/Amgen, 101 Reykjavik, Iceland. unnurth@decode.is
Nature
|May 7, 2013
まとめ
LGR4遺伝子の希少な変異により,骨粗鬆症や骨折のリスクが大きく増加します. この発見は,骨密度調節と関連する健康状態に関する新しい洞察を提供します.
科学分野:
- 遺伝学 遺伝学とは
- 骨粗鬆症の研究について
- 人間の生理学 人間生理学
背景:
- 低骨密度 (BMD) は,骨粗鬆症の重要な指標である.
- これまでの全ゲノム関連研究では,定量的な特徴としてのBMDに焦点を当て,軽微な効果を持つ一般的な変異を特定しました.
- 病理的に低いBMDにおける希少変異の役割は,まだあまり理解されていません.
研究 の 目的:
- 病理的に低いBMDのリスクに直接影響する遺伝的変異を特定し,二分性特質として扱います.
- 特定された突然変異の機能的影響を調査する.
- 関連遺伝子の潜在的なプレオトロピク効果を探求する.
主な方法:
- アイスランド人の全ゲノム配列解析.
- リスク変数を特定するための二分的な特徴としてのBMDの分析.
- LGR4遺伝子の特定された突然変異の機能的特徴.
- 変異媒体のフェノタイプ分析 変異媒体のフェノタイプ分析
主要な成果:
- LGR4遺伝子の珍しいナンセンス変異 (c.376C>T) が特定され,低BMDと骨粗鬆性骨折と強く関連しています.
- この突然変異は,LGR4タンパク質の機能を完全に失うことにつながります.
- キャリアはまた,電解質の不均衡,初潮の遅延,テストステロンの減少,特定の癌のリスクの増加を示した.
結論:
- LGR4遺伝子は骨の健康に重要な役割を果たし,骨粗鬆症治療の潜在的なターゲットです.
- 特定された突然変異は,複数の生理系に影響を及ぼすプレオトロピック効果を持っています.
- この研究は,複雑な病気を理解するために,まれな変異を調査することの重要性を強調しています.
関連する概念動画
02:41Lethal Alleles
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
02:27Nonsense-mediated mRNA Decay
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
02:27Nonsense-mediated mRNA Decay
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
03:18Non-LTR Retrotransposons
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
01:31Translation
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life